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FOS 基因相关免疫浸润特征在腹主动脉瘤血管周围脂肪组织中的表达。

FOS gene associated immune infiltration signature in perivascular adipose tissues of abdominal aortic aneurysm.

机构信息

School of Basic Medicine, Gannan Medical University, Ganzhou, China.

College of Biology and Agriculture, Zunyi Normal College, Zunyi, China.

出版信息

Gene. 2022 Jul 15;831:146576. doi: 10.1016/j.gene.2022.146576. Epub 2022 May 11.

Abstract

Abdominal aortic aneurysms (AAA) are pathological dilations in local aortic wall. The inflammatory infiltrates of the perivascular adipose tissue (PAT) surrounding AAAs were associated with AAAs and have been shown to contribute vascular pathology. However, the mechanism by which PAT inflammation contributes to vascular pathology in AAA remains to be clarified. This study aimed to explore the association between immune cell infiltration and key gene expression profile in PAT of AAA. For that, a gene expression dataset of human dilated perivascular adipose tissue (dPAT), non-dilated perivascular adipose tissue (ndPAT), subcutaneous abdominal fat (SAF) and omental-visceral fat (OVF) samples, as well as another microarray dataset of the abdominal perivascular adipose tissue in peripheral artery disease patients were downloaded from GEO database for analysis in this study. The CIBERSORT algorithm, weighted gene co-expression network analysis (WGCNA) and LASSO algorithm were used for the identification of immune infiltration, immune-related genes and the development of diagnostic signature. Our data discovered a significant higher proportion of activated mast cells and follicular helper T (Tfh) cells in dPAT than ndPAT, OVT and SAF samples. Moreover, AP-1 family members (FOS, FOSB, ATF3, JUN and JUNB) were found to compose the hub genes of purple module in WGCNA. Among them, FOS gene acts as a higher efficient marker to discriminate dPAT from ndPAT, OVT and SAF in AAA. Meanwhile, the expression profiles of the AP-1 family members are all significantly positive correlated with activated mast cell, plasma cell and Tfh cell infiltration in dPAT of AAA. Therefore, in the PAT surrounding AAA, the signature of inflammatory infiltration might be represented by a FOS-dominated cell network consist of activated mast cell, plasma cell and Tfh cell. Given the complicated etiology of AAA, our results are likely to shed new light on the pathophysiologic mechanism of AAA influenced by the local dPAT.

摘要

腹主动脉瘤(AAA)是局部主动脉壁的病理性扩张。AAA 周围血管周围脂肪组织(PAT)的炎症浸润与 AAA 相关,并已被证明有助于血管病理学。然而,PAT 炎症如何导致 AAA 中的血管病理学仍不清楚。本研究旨在探讨 AAA 中 PAT 中免疫细胞浸润与关键基因表达谱之间的关联。为此,从 GEO 数据库下载了人类扩张性血管周围脂肪组织(dPAT)、非扩张性血管周围脂肪组织(ndPAT)、皮下腹部脂肪(SAF)和网膜内脏脂肪(OVF)样本的基因表达数据集,以及另一个外周动脉疾病患者腹部血管周围脂肪组织的微阵列数据集,用于本研究的分析。使用 CIBERSORT 算法、加权基因共表达网络分析(WGCNA)和 LASSO 算法识别免疫浸润、免疫相关基因,并开发诊断特征。我们的数据发现,dPAT 中的活化肥大细胞和滤泡辅助 T(Tfh)细胞的比例明显高于 ndPAT、OVT 和 SAF 样本。此外,AP-1 家族成员(FOS、FOSB、ATF3、JUN 和 JUNB)被发现是 WGCNA 中紫色模块的核心基因。其中,FOS 基因是区分 AAA 中 dPAT 和 ndPAT、OVT 和 SAF 的更高效率标记物。同时,AP-1 家族成员的表达谱与 AAA 中 dPAT 中活化肥大细胞、浆细胞和 Tfh 细胞浸润均呈显著正相关。因此,在 AAA 周围的 PAT 中,炎症浸润的特征可能由以 FOS 为主导的细胞网络代表,该网络由活化的肥大细胞、浆细胞和 Tfh 细胞组成。鉴于 AAA 的复杂病因,我们的结果可能为受局部 dPAT 影响的 AAA 病理生理机制提供新的见解。

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